Hormonal
GIP receptor antagonism, when combined with GLP-1 receptor agonism, produces superior weight loss and glycemic control compared to GLP-1 receptor agonism alone.
Current research indicates that combining a GIP receptor antagonist with a GLP-1 agonist (like the investigational drug AMG133) leads to greater weight loss and better blood sugar control than using a GLP-1 agonist alone. This benefit is seen in clinical trials with sustained effects, though the exact mechanism of the GIP part's contribution to weight loss is not fully understood.
Novel insights into GIP receptor targeting treatment reveal that both GIP receptor antagonists and agonists, when combined with glucagon like peptide 1 (GLP-1) receptor activation, are associated with improved glycemic control and weight loss.
Why this rating
Supported by preclinical data in monkeys/mice and Phase 1/2 human trials for AMG133, though long-term human data is still emerging.
Source
The evolution of the therapeutic concept ‘GIP receptor antagonism’
Frederikke Koefoed-Hansen et al. · Frontiers in Endocrinology · 2025
DOI 10.3389/fendo.2025.1570603
More from this paper
- Endogenous GIP acts as an incretin that potentiates glucose-stimulated insulin secretion, and its inhibition via GIP receptor antagonists reveals this physiological role.Strong
- Genetic loss-of-function variants of the GIP receptor are associated with lower body mass index (BMI) and reduced obesity prevalence in humans.Good
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